Fecal microbiota transplantation for refractory chronic graft-versus-host disease after allogeneic hematopoietic cell transplantation: a pilot open-label, non-placebo-controlled study

Dysbiosis of the intestinal microbiota plays a crucial role in the initiation and development of graft-versus-host disease (GVHD). Fecal microbiota transplantation (FMT) has been reported to be effective for refractory acute GVHD; however, whether FMT is effective for refractory chronic GVHD (cGVHD) remains unknown. To investigate the efficacy and safety of FMT for refractory cGVHD and the underlying mechanism, 12 patients with refractory cGVHD received FMT via colonoscopy, and the response was evaluated at 12 weeks after FMT. Among the 12 patients who underwent FMT, 1 patient achieved a complete response, and 5 patients achieved a partial response. Patients with refractory cGVHD presented lower α diversity and higher abundance of Escherichia-Shigella and Enterobacteriaceae. FMT increased gut microbial diversity, increased the abundance of short-chain fatty acid (SCFA)-producing bacteria, and decreased the abundance of Escherichia-Shigella and Enterobacteriaceae in responder patients. Moreover, it increased SCFA levels in fecal samples from the responder group and promoted the expansion of peripheral CD4+CD127- regulatory T (Treg) cells. Colon pathological examination revealed that CD4+ T and CD19+ B cell infiltration decreased and that CD4+ Treg infiltration increased after FMT. The results of the present study suggest that FMT is feasible and deserves further investigation for use in patients with refractory cGVHD. ClinicalTrials.gov (NCT06938165).